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Galectin-4 (Gal-4) is a β-galactoside–binding protein belonging to the galectin family. Although Gal-4 is known to be involved in several physiologic processes of the gastrointestinal tract, its immunomodulatory roles remain unclear. In this study, we investigated whether Gal-4 influences the function of M1 and M2 macrophages. Gal-4 treatment drove more robust changes in the gene expression of M2 macrophages compared to M1 macrophages. Antiviral immune response–related genes were significantly upregulated in Gal-4–treated M2 macrophages. Gal-4 significantly enhanced the immunostimulatory activity of M2 macrophages upon Toll-like receptor 7 stimulation or infection with lymphocytic choriomeningitis virus (LCMV). Moreover, the antibody production against LCMV infection and the antiviral CD4+ T-cell responses, but not the antiviral CD8+ T-cell responses, were greatly increased by Gal-4–treated M2 macrophages in vivo. The present results indicate that Gal-4 enhances the ability of M2 macrophages to promote antiviral CD4+ T-cell responses. Thus, Gal-4 could be used to boost antiviral immune responses.

To (1) evaluate the optimal drill orientation of the anterolateral ligament (ALL) femoral tunnel to minimize collision with the anterior cruciate ligament (ACL) femoral tunnel during anatomical ACL reconstruction according to the need for far-cortex drilling and (2) investigate the geometric factors that affect tunnel collision secondary to drill orientation of the ALL femoral tunnel.A three-dimensional femoral model of patients who underwent anatomical single-bundle ACL reconstruction between 2015 and 2016 was constructed, and the geometric factors were evaluated. Virtual ALL femoral tunnels were created to simulate 45 drilling conditions. For each condition, whether the virtual ALL femoral tunnel and its trajectory violated the femoral cortex and the minimum distance between tunnels was investigated.Thirty-nine subjects were included. Overall violation rates of the femoral cortex by the ALL tunnels and its trajectories were 11.1% (195 of 1755 conditions) and 40.7% (714 of 1755 conditions), respectively. A drilling angle of axial 0° and coronal - 40° showed the longest minimum distance between tunnels without femoral cortex violation by the ALL tunnel (6.3 ± 4.0 mm; collision rate 2.6% [1 of 39 subjects]). With simultaneous consideration of the ALL tunnel's trajectory representing far-cortex drilling, a drill angle of axial 40° and coronal 10° showed the longest minimum distance between tunnels without femoral cortex violation (0.6 ± 3.9 mm; collision rate 38.5% [15 of 39 subjects]). For surgical techniques requiring far-cortex drilling, regression analyses were performed on geometric factors that could affect tunnel collision, which revealed that the sagittal inclination angle of the ACL and the distance between the ACL femoral tunnel's outlet and ALL's femoral attachment were associated with tunnel collision.The optimal drill orientations of the ALL femoral tunnel to minimize collision with the ACL femoral tunnel were axial 0° and coronal - 40° for surgical techniques not requiring far-cortex drilling and axial 40° and coronal 10° for techniques requiring far-cortex drilling. For techniques requiring far-cortex drilling, additional adjustment for orientation of the ACL femoral tunnel is required to reduce the risk of tunnel collision. Therefore, an individualized surgical strategy should be applied according to the graft fixation method of the ALL femoral tunnel.

Tiron is a potent antioxidant that counters the pathological effects of reactive oxygen species (ROS) production due to oxidative stress in various cell types. We examined the effects of tiron on mitochondrial function and osteoblastic differentiation in human periosteum-derived cells (hPDCs). Tiron increased mitochondrial activity and decreased senescence-associated β-galactosidase activity in hPDCs; however, it had a detrimental effect on osteoblastic differentiation by reducing alkaline phosphatase (ALP) activity and alizarin red-positive mineralization, regardless of H2O2 treatment. Osteoblast-differentiating hPDCs displayed increased ROS production compared with non-differentiating hPDCs, and treatment with tiron reduced ROS production in the differentiating cells. Antioxidants decreased the rates of oxygen consumption and ATP production, which are increased in hPDCs during osteoblastic differentiation. In addition, treatment with tiron reduced the levels of most mitochondrial proteins, which are increased in hPDCs during culture in osteogenic induction medium. These results suggest that tiron exerts negative effects on the osteoblastic differentiation of hPDCs by causing mitochondrial dysfunction.

We sequenced the complete mitochondrial genome of the copepod

With the emergence of COVID‐19 worldwide, interest in blended learning in higher education is rapidly increasing Despite the fact that the unipolar view that satisfaction and dissatisfaction are measured separately has been emphasized in higher education, fewer efforts have been made in a blended learning context Therefore, this study attempts to document the unipolar view of satisfaction and dissatisfaction in a blended learning context by adopting the Kano model More specifically, the objectives of this study is to (1) conceptualize online and offline service dimensions in blended learning, (2) examine the asymmetric effect between satisfaction and dissatisfaction, and (3) apply those results to the Kano model The following results are reported: (1) system quality and assurance are symmetric, functioning as a satisfier;and (2) information quality, responsiveness, and tangibility are asymmetric, functioning as a delighter Theoretical and practical implications are addressed [ABSTRACT FROM AUTHOR] Copyright of Educational Measurement: Issues & Practice is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

The influenza A virus (IAV) has caused several pandemics, and therefore there are many ongoing efforts to identify novel antiviral therapeutic strategies including vaccines and antiviral drugs. However, influenza viruses continuously undergo antigenic drift and shift, resulting in the emergence of mutated viruses. In turn, this decreases the efficiency of existing vaccines and antiviral drugs to control IAV infection. Therefore, this study sought to identify alternative therapeutic strategies targeting host cell factors rather than viruses to avoid infection by mutated viruses. Particularly, we investigated the role of KIF20A that is one of kinesin superfamily proteins in the replication of IAV. The KIF20A increased viral protein levels in IAV-infected cells by regulating the initial entry stage during viral infection. Furthermore, the KIF20A inhibitor significantly suppressed viral replication, which protected mice from morbidity and mortality. Therefore, our findings demonstrated that KIF20A is highly involved in the viral replication process and viral propagation both in vitro and in vivo, and could thus be used as a target for the development of novel antiviral drugs.

The present study aims to conceptualize service quality and perceived value in the context of blended learning by redefining and modifying the existing SERVQUAL model, reviewing prior marketing literature on perceived value, and examining the relationships between service quality, perceived value, and student satisfaction. The sample was restricted to colleges in South Korea, where blended learning programs have started to receive much attention. We examined our hypotheses by using regression analysis via the statistical programs Amos 22.0 and SPSS 23.0. The following results are produced. First, the conceptualization of service quality and perceived value was confirmed. Second, the different effects of online and offline service quality on each perceived value are confirmed. Offline service quality is more effective in generating perceived epistemic value, perceived social value, and perceived emotional value than online service quality, whereas online service quality is more effective in triggering perceived conditional value than offline service quality. Finally, perceived emotional value and perceived conditional value are the important determinants of student satisfaction. We address the theoretical implications that (1) service quality and perceived value are conceptualized through modification, refinement, and empirical testing and develop a multidimensional scale for service quality and perceived value, and (2) the sequential and causal relationships among service quality, perceived value, and student satisfaction are confirmed. Practically, we expect that our measurement scales for service quality and perceived value, which have high validity and reliability, can serve as diagnostic tools for blended learning program evaluation from students' perspective.

Seasonal flu is an infectious disease of the respiratory tract caused by influenza viruses. The development of anti-influenza drugs has significantly reduced the threat from the influenza virus; however, frequent mutations of this negative RNA virus result in antiviral-resistant strains, and constantly intimidate the human race. Thus, identifying novel therapeutic targets for the prevention and treatment of influenza virus infections is critical. We aimed to determine whether the kinesin superfamily protein 11 (KIF11) inhibitors, monastrol and K858, inhibit viral cytopathogenesis and influenza A virus (IAV) replication. When MDCK or HEK293 cells were treated with monastrol and K858 that did not induce significant cytotoxicity, IAV-induced cytopathic effect was attenuated significantly. Furthermore, these inhibitors effectively suppressed the production of viral RNA, proteins, and infectious viral particles. Inhibition of KIF11 activity effectively attenuates virus-mediated cytopathic effect and suppresses viral replication. Hence, KIF11 is a potential therapeutic target against the influenza virus.

Chronic viral infections are often established by the exploitation of immune-regulatory mechanisms that result in nonfunctional T cell responses. Viruses that establish persistent infections remain a serious threat to human health. Sphingosine kinase 2 (SphK2) generates sphingosine 1-phosphate, which is a molecule known to regulate multiple cellular processes. However, little is known about SphK2’s role during the host immune responses to viral infection. Here, we demonstrate that SphK2 functions during lymphocytic choriomeningitis virus Cl 13 (LCMV Cl 13) infection to limit T cell immune pathology, which subsequently aids in the establishment of virus-induced immunosuppression and the resultant viral persistence. The infection of Sphk2-deficient (Sphk2(–/–)) mice with LCMV Cl 13 led to the development of nephropathy and mortality via T cell–mediated immunopathology. Following LCMV infection, Sphk2(–/–) CD4(+) T cells displayed increased activity and proliferation, and these cells promoted overactive LCMV Cl 13–specific CD8(+) T cell responses. Notably, oral instillation of an SphK2-selective inhibitor promoted protective T cell responses and accelerated the termination of LCMV Cl 13 persistence in mice. Thus, SphK2 is indicated as an immunotherapeutic target for the control of persistent viral infections.

Embryonic stem cells (ESCs) possess specific gene expression patterns that confer the ability to proliferate indefinitely and enable pluripotency, which allows ESCs to differentiate into diverse cell types in response to developmental signals. Compared to differentiated cells, ESCs harbor an elevated level of homologous recombination (HR)-related proteins and exhibit exceptional cell cycle control, characterized by a high proliferation rate and a prolonged S phase. HR is involved in several aspects of chromosome maintenance. For instance, HR repairs impaired chromosomes and prevents the collapse of DNA replication forks during cell proliferation. Thus, HR is essential for the maintenance of genomic integrity and prevents cellular dysregulation and lethal events. In addition, abundant HR proteins in the prolonged S phase can efficiently protect ESCs from external damages and protect against genomic instability caused by DNA breaks, facilitating rapid and accurate DNA break repair following chromosome duplication. The maintenance of genome integrity is key to preserving the functions of ESCs and reducing the risks of cancer development, cell cycle arrest, and abnormal replication. Here, we review the fundamental links between the stem cell-specific HR process and DNA damage response as well as the different strategies employed by ESCs to maintain genomic integrity., Embryonic stem cells: extra protection for DNA Embryonic stem cells (ESCs), which give rise to the many specialized cells of the body, have highly effective molecular processes of DNA maintenance and repair which protect their genetic information from damage. Keun Pil Kim and colleagues at Chung-Ang University, Seoul, South Korea, review the strategies found in ESCs to maintain the integrity of their DNA as they develop and multiply. A key feature is the process of homologous recombination (HR) in which one copy of a section of DNA acts as the template allowing a damaged version of the DNA to be repaired. HR also facilitates swapping of sections of DNA when sperm and egg cells form, promoting genetic diversity. HR appears to be especially significant in maintaining ESC DNA as ESCs possess higher levels of key proteins involved in its maintenance and regulation.

Purpose To compare the efficacies of mirabegron 50 mg addition after alpha-adrenoreceptor blocker in terms of reducing storage symptoms in patients with BPH. Materials and methods Fifty-eight patients that had been taking alpha-adrenoreceptor blocker for more than 8 weeks, but had an OABSS of greater than 3 points, were initially enrolled. One group added any alpha-adrenoreceptor blocker with mirabegron 50 mg (n=39; the mirabegron group) and the other group received alpha-adrenoreceptor blocker only (n=19; the control group) for 8 weeks. Results In the control group, mean total IPSS decreased from 15.7 to 13.1 (p=0.298) and in mirabegron group, mean total IPSS decreased from 19.4 to 16.5 (p=0.024). Mean storage symptom scores reduced in the control and mirabegron groups from 8.5 to 7.9 (p=0.584) and from 9.1 to 7.6 (p=0.015), respectively, and mean QoL scores from 3.7 to 3.1 (p=0.052) and 3.6 to 3.2 (p=0.027), respectively. Mean overall OABSS in the control and mirabegron groups reduced from 8.4 to 7.2 (p=0.173) and from 8.8 to 7.3, respectively (p=0.005); mean OABSS Q3 from 3.6 to 2.9 (p=0.073) and from 3.5 to 2.7 (p=0.002), respectively; and mean OABSS Q4 from 2.4 to 2.0 (p=0.306) and from 2.7 to 2.0 (p=0.016), respectively. The change of mean Qmax and PVR was insignificant in 2 groups. Conclusions IPSS total scores, storage symptom scores, QoL, overall OABSS, OABSS Q3 and Q4 were more improved significantly by alpha-adrenoreceptor blocker with mirabegron 50 mg in BPH patients with persistent overactive symptoms. Mirabegron 50 mg addition is considered to patients with persistent storage symptoms after alpha-adrenoreceptor blocker.

The influenza virus is one of the major public health threats. However, the development of efficient vaccines and therapeutic drugs to combat this virus is greatly limited by its frequent genetic mutations. Because of this, targeting the host factors required for influenza virus replication may be a more effective strategy for inhibiting a broader spectrum of variants. Here, we demonstrated that inhibition of a motor protein kinesin family member 18A (KIF18A) suppresses the replication of the influenza A virus (IAV). The expression of KIF18A in host cells was increased following IAV infection. Intriguingly, treatment with the selective and ATP‐competitive mitotic kinesin KIF18A inhibitor BTB‐1 substantially decreased the expression of viral RNAs and proteins, and the production of infectious viral particles, while overexpression of KIF18A enhanced the replication of IAV. Importantly, BTB‐1 treatment attenuated the activation of AKT, p38 MAPK, SAPK and Ran‐binding protein 3 (RanBP3), which led to the prevention of the nuclear export of viral ribonucleoprotein complexes. Notably, administration of BTB‐1 greatly improved the viability of IAV‐infected mice. Collectively, our results unveiled a beneficial role of KIF18A in IAV replication, and thus, KIF18A could be a potential therapeutic target for the control of IAV infection.

Background It is unclear whether different anterior cruciate ligament (ACL) graft trajectories in the distal femur would have different effects on stress generated within the distal femur around the femoral tunnel during knee motion. Thus, the purpose of this study was to determine differences in stress patterns around the femoral tunnel created by trans-portal (TP) vs. modified trans-tibial (TT) technique in anatomical ACL reconstruction at different knee flexion angles. Methods Twelve male subjects’ right knees were scanned with a high-resolution computed tomography (CT) scanner (slice thickness: 1 mm) at four different knee flexion angles (0°, 45°, 90°, and 135°). Three-dimensional (3D) models of these four different flexion angles were created and manipulated with several modelling programs. For the TP group, the virtual femoral tunnelling procedure was performed in a 135° flexion model from the low far anteromedial (AM) portal. For the modified TT group, the same knee models were drilled through the modified TT technique at 90° of flexion separately. Virtual grafts under tension of 40 N were put into corresponding bone tunnel and fixed at the outer aperture of femoral tunnels to simulate the suspensory fixation, followed by fixation of the grafts at the middle of tibial tunnels in the 0° knee flexion models. Finally, the models were exported to a finite element analysis package and analysed using ABAQUS/Explicit code (ABAQUS, USA) to monitor the stress occurring at the node where stress distribution occurred most significantly in the femoral bone around the bone tunnel. Results In general, both groups showed a high stress distribution in bony structures around inner and outer orifices of the femoral tunnel. Mean maximal stresses occurring at the lateral femoral condyle around the inner orifice of the femoral tunnel in the TP group were found to be significantly greater than those in the modified TT group at all flexion angles except 90° of flexion. Mean maximal stresses monitored around the outer orifice of the femoral tunnel in the TP group were also significantly greater than those in the modified TT group at all flexion angles. Conclusions Different tunnelling technologies could yield different stress patterns in the lateral femoral condyle around the femoral tunnel. During knee motion, higher stresses were noticed in the TP group than in the modified TT group, especially around inner and outer orifices of the tunnel. Position of the tunnel after reconstruction with the TP technique can have a greater effect on the stress increase in the femur compared to that with the modified TT technique.

To compare the femoral tunnel characteristics using a rigid versus flexible reamer during anterior cruciate ligament reconstruction. It was hypothesized that the employment of a flexible reamer along with femoral tunnel would exhibit longer tunnel length and more acute femoral graft tunnel angle compared to the case of a rigid reamer. The study population included 28 patients who underwent anatomical single-bundle anterior cruciate ligament reconstruction using transportal technique and were able to take postoperative computed tomography (CT) evaluation. Of these, the femoral tunnel of 14 cases was drilled with a flexible reamer (group I) and in another 14 cases drill was performed with a conventional rigid reamer (group II). The femoral tunnel in group I was made at 90° of knee flexion. In group II, the femoral tunnel was created at 120° of knee flexion. The parameters of the femoral tunnels were compared in terms of the femoral tunnel length and femoral graft tunnel angle. Special software was used to create and manipulate (3-D) 3-dimensional knee models. The difference in the mean femoral tunnel locations expressed in percentage distance between the 2 groups was not significantly different. The mean femoral tunnel length of group I was significantly longer than that of group II, (P = .03, 36.7 ± 2.9 vs 32.9 ± 9.0 mm). The angle formed by the femoral tunnel and the graft in group I was significantly smaller than in group II (P = .01, 109.8° ± 9.4° vs 118.1° ± 7.2°). Our data suggest that the flexible reamer can provide sufficient tunnel length for the suspensory fixation with a fixed loop. Whereas, the femoral graft-tunnel angle through flexible reaming at 90° of knee flexion was more acute compared to rigid reaming at 120° of knee flexion. Study Design: level of evidence III

Elaeocarpus sylvestris var. ellipticus (ES), a plant that grows in Taiwan, Japan, and Jeju Island in Korea. ES root bark, known as "sanduyoung," has long been used in traditional oriental medicine. ES is also traditionally used to treat anxiety, asthma, arthritis, stress, depression, palpitation, nerve pain, epilepsy, migraine, hypertension, liver diseases, diabetes, and malaria. However, lack of efficacy and mechanism studies on ES.In the present study, we aim to investigate the VZV-antiviral efficacy, pain suppression, and the anti-inflammatory and antipyretic effects of ES.and methods: Inhibition of VZV was evaluated by hollow fiber assays. Analgesic and antipyretic experiments were conducted using ICR mice and SD Rats, and anti-inflammatory experiments were conducted using Raw264.7 cells.To evaluate the efficacy of ESE against VZV, we conducted antiviral tests. ESE inhibited cell death by disrupting virus and gene expression related to invasion and replication. In addition, ESE suppressed the pain response as measured by writhing and formalin tests and suppressed LPS-induced inflammatory fever. Further, ESE inhibited the phosphorylation of IκB and NF-κB in LPS-induced Raw264.7 cells and expression of COX-2, iNOS, IL-1β, IL-6, and TNF-α.E. sylvestris shows potential as a source of medicine. ESE had a direct effect on VZV and an inhibitory effect on the pain and inflammation caused by VZV infection.

The purpose of the study was to determine the change in the graft bending angles at the femoral and tibial tunnel aperture in single-bundle posterior cruciate ligament (PCL) reconstruction. It was hypothesized that different knee flexion and different tunnel directions may affect changes of the femoral and tibial graft bending angle. The right knees of 12 male subjects were scanned with a high-resolution computed tomography scanner at 4 different knee flexion angles (0°, 45°, 90° and 135°). To begin with, the 3D knee models were created and manipulated with the use of several modeling programs. Single-bundle PCL reconstruction was then virtually conducted in a 90° flexion model: The femoral and tibial graft bending angle, according to the various knee flexion angles, was calculated using a special software program. The femoral graft bending angle significantly decreased as the knee flexion increased between 0° and 135° (all p

The blue-green alga Spirulina maxima is a microscopic filamentous cyanobacterium. Spirulina was recently reported to elicit beneficial effects such as reducing cholesterol and inducing weight loss; however, its effects on inflammation are unknown. To determine the effect of S. maxima extract (SME) on innate immunity, we investigated the NLRP3 inflammasome activation, which is a multiprotein scaffolding complex that plays important roles in innate immune responses to many pathogenic infections in macrophages. SME suppressed lipopolysaccharide (LPS)-induced upregulation of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-12, IL-1β, and IL-18 in RAW264.7 cells. In addition, SME attenuated LPS-induced NLRP3 inflammasome activation, and thus pro-IL-1β could not be cleaved to IL-1β by activated caspase-1, which is activated by the NLRP3 inflammasome in RAW264.7 cells. Moreover, SME inhibited LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) in RAW264.7 cells, and attenuated the generation of ERK1 induced-reactive oxygen species (ROS), resulting in decreased expression of NF-κB. These findings suggest that SME suppresses the effects of the NLRP3 inflammasome via regulation of extracellular signal-regulated kinase (ERK). In summary, we demonstrated that SME prevents activation of the NLRP3 inflammasome by inhibiting ERK signaling.

Obesity is a global chronic disease linked to various diseases. Increased consumption of added sugars, especially in beverages, is a key contributor to the obesity epidemic. It is essential to reduce or replace sugar intake with low-calorie sweeteners. Here, a natural sweet protein, 3M-brazzein, was investigated as a possible sugar substitute. Mice were exposed to 3M-brazzein or 10% sucrose of equivalent sweetness, in drinking water to mimic human obesity development over 15 weeks. Consumption of 3M-brazzein in liquid form did not cause adiposity hypertrophy, resulting in 33.1 ± 0.4 g body weight and 0.90 ± 0.2 mm fat accumulation, which were 35.9 ± 0.7 g (p = 0.0094) and 1.53 ± 0.067 mm (p = 0.0031), respectively, for sucrose supplement. Additionally, 3M-brazzein did not disrupt glucose homeostasis or affect insulin resistance and inflammation. Due to its naturally low-calorie content, 3M-brazzein could also be a potential sugar substitute that reduces adiposity.

Myofibroblasts are the major cell type that is responsible for increase in the mechanical stiffness in fibrotic tissues. It has well documented that the TGF-β/Smad axis is required for myofibroblast differentiation under the rigid substrate condition. However, the mechanism driving myofibroblast differentiation in soft substrates remains unknown. In this research, we demonstrated that interaction of yes-associated protein (YAP) and acetylated microtubule via dynein, a microtubule motor protein drives nuclear localization of YAP in the soft matrix, which in turn increased TGF-β1-induced transcriptional activity of Smad for myofibroblast differentiation. Pharmacological and genetical disruption of dynein impaired the nuclear translocation of YAP and decreased the TGF-β1-induced Smad activity even though phosphorylation and nuclear localization of Smad occurred normally in α-tubulin acetyltransferase 1 (α-TAT1) knockout cell. Moreover, microtubule acetylation prominently appeared in the fibroblast-like cells nearby the blood vessel in the fibrotic liver induced by CCl4 administration, which was conversely decreased by TGF-β receptor inhibitor. As a result, quantitative inhibition of microtubule acetylation may be suggested as a new target for overcoming fibrotic diseases.

To investigate whether earthworm cellulases contribute to the innate immune system, the responsiveness of cellulase activity and mRNA expression to bacterial challenge was examined by zymography and RNA sequencing. A zymographic analysis revealed that the activity levels of earthworm cellulases were upregulated in response to either a bacterial (Bacillus subtilis or Escherichia coli) or LPS challenge. After the challenge, significant increases in cellulase 1 and cellulase 2 activity levels were observed within 8–16 and 16–24 h, respectively. In the coelomic fluid, both activities were significantly upregulated at 8 h post-injection with B. subtilis. Based on RNA sequencing, cellulase-related mRNAs encoding beta-1,4-endoglucanases were upregulated by 3-fold within 6 h after B. subtilis injection. Our results clearly demonstrated that earthworm cellulases are upregulated by bacterial challenge at the mRNA and protein levels. These results support the view that earthworm cellulases act as inducible humoral effectors of innate immunity against bacterial infection.

KIF18A is a kinesin family member that is involved in various cellular processes including cell division, cell transformation, and carcinogenesis. However, its possible role in the regulation of host immunity has not been examined. The aim of this study is to investigate the functional role of KIF18A in the differentiation and activation of dendritic cells (DCs) that are the most efficient antigen-presenting cells. A bioinformatic analysis of the KIF18A gene family was performed to understand its sequence variability and evolutionary history. To inhibit KIF18A activity, a highly specific small molecule inhibitor for KIF18A, BTB-1 was used. DCs were differentiated from mouse bone marrow (BM) cells from 6 to 7 week old C57BL/6 mice with recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF). Expression of KIF18A was measured by Western blotting. The surface expression of differentiation and activation markers on DCs were analyzed by flow cytometry. The phylogenetic analysis revealed that the KIF18A gene family is remarkably conserved across vertebrates. Interestingly, the expression of KIF18A was increased as BM precursor cells differentiated into DCs. BTB-1 treatment strongly inhibited the differentiation of BM cells into DCs in a dose-dependent manner. Furthermore, treatment of immature DCs with BTB-1 significantly impaired the expression of activation markers on DCs including MHC class I, CD80, and CD86 upon TLR4 or TLR7 treatment. Our results reveal that KIF18A is a critical DC differentiation and activation regulator. Therefore, KIF18A could be a potential therapeutic target for immune-mediated disorders.

Background: Panax ginseng Meyer is known as a conventional herbal medicine, and ginsenoside Rg1, a steroid glycoside, is one of its components. Although Rg1 has been proved to have an antiobesity effect, the mechanism of this effect and whether it involves adipose browning have not been elucidated. Methods: 3T3-L1 and subcutaneous white adipocytes from mice were used to access the thermogenic effect of Rg1. Adipose mitochondria and uncoupling protein 1 (UCP1) expression were analyzed by immunofluorescence. Protein level and mRNA of UCP1 were also evaluated by Western blotting and real-time polymerase chain reaction, respectively. Results: Rg1 dramatically enhanced expression of brown adipocyte–specific markers, such as UCP1 and fatty acid oxidation genes, including carnitine palmitoyltransferase 1. In addition, it modulated lipid metabolism, activated 5′ adenosine monophosphate (AMP)-activated protein kinase, and promoted lipid droplet dispersion. Conclusions: Rg1 increases UCP1 expression and mitochondrial biogenesis in 3T3-L1 and subcutaneous white adipose cells isolated from C57BL/6 mice. We suggest that Rg1 exerts its antiobesity effects by promoting adipocyte browning through activation of the AMP-activated protein kinase pathway. Keywords: Adipocytes, Browning, Ginsenoside Rg1, Thermogenesis, Uncoupling protein 1

While college interdisciplinary programs are widespread in South Korea, little is known about what factors can increase college student satisfaction and/or dissatisfaction or whether satisfaction and dissatisfaction are opposite or different constructs. Thus, applying the Stimulus-Organization-Response theory and Kano model, this study seeks to employ service fairness and service quality as diagnostic tools to predict satisfaction and dissatisfaction, examine the asymmetric effect of those attributes on both emotions, and investigate how those emotions are related to the intention of continuing the program. The following results were produced: (1) personal and administrative quality are positively related to satisfaction and negatively related to dissatisfaction, working as satisfiers; (2) procedural fairness is negatively related to both satisfaction and dissatisfaction, working as a dissatisfier; (3) distributive and interactional fairness are positively related to satisfaction, working as delighters; and (4) satisfaction and dissatisfaction are significantly related to continuance intention in an opposite direction.

Influenza A virus (IAV) continues to threaten human health. To date, two classes of antiviral drugs have been approved to treat IAV infection, but the continuous emergence of the drug-resistant IAV mutant reinforces the need to develop new antiviral drugs. In this study, we aimed to investigate the anti-IAV activity of an aqueous mixture of Agrimonia pilosa and Galla rhois extracts (APRG64). We demonstrated that APRG64 significantly reduced the IAV-induced cytopathic effect, the transcription/expression of viral proteins, and the production of infectious viral particles. Among nine major components of APRG64, apigenin was identified as the main ingredient responsible for the anti-IAV activity. Interestingly, APRG64 and apigenin inhibited the cell attachment and entry of virus and polymerase activity. Importantly, intranasal administration of APRG64 or apigenin strongly reduced viral loads in the lungs of IAV-infected mice. Furthermore, oral administration of APRG64 significantly reduced the level of viral RNAs and the expression level of pro-inflammatory cytokines in the lungs, which protected mice from IAV-induced mortality. In conclusion, APRG64 could be an attractive antiviral drug to treat IAV infection.

Zanthoxylum piperitum has been used as a traditional Asian medicine to treat hypertension, stroke, bruise and muscle pain. It has been known to induce detoxification; affect anti-bacterial, anti-oxidant, and tyrosinase activity; inhibit osteosarcoma proliferation; anti-osteoarthritis inflammation. In this study, we aim to identify the therapeutic effect of Z. piperitum 90% EtOH extract (ZPE-LR) on rheumatoid arthritis.We investigated the anti-rheumatoid arthritis and -immunomodulatory activities of the ZPE-LR in collagen-induced arthritic (CIA) mice, a rheumatoid arthritis animal model. In order to assess the analgesic effects of ZPE-LR in vivo, acetic acid injection, formaldehyde injection, hot plate model was used. The mechanism for anti-inflammatory activity of ZPE-LR was identified with LPS-stimulated Raw 264.7 cells.Pharmacologically, oral administration of ZPE-LR into CIA mice resulted in a significant and dose-dependent decrease in clinical arthritis score and paw swelling compared to untreated negative control. Pathologic examination showed that ZPE-LR prevented morphological change in cartilage and destruction of phalanges in CIA mice. This protective effect was associated with reduced pain, inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6, as well as COX-2 and iNOS expression. Furthermore, reduction of phosphor-ERK and BDNF indicates a novel rheumatoid arthritis-regulating mechanism by ZPE-LR treatment.These data suggest that the administration of ZPE-LR remarkably inhibited CIA progression and might be helpful in suppressing inflammation and pain in rheumatoid arthritis.

Elaeocarpus sylvestris (Lour.) Poir. (Elaeocarpaceae) belongs to a genus of tropical and semitropical evergreen trees, which has known biological activities such as antiviral and immunomodulatory activities. However, its antiviral potential against influenza virus infection remains unknown.In this study, we investigated the antiviral activity of the 50% aqueous ethanolic extract of E. sylvestris (ESE) against influenza A virus (IAV) infection, which could lead to the development of novel phytomedicine to treat influenza virus infection.To investigate the in vitro antiviral activity of ESE and its main ingredients, 1,​2,​3,​4,​6-​penta-​O-​galloyl-β-d-glucose (PGG) and geraniin (GE), the levels of viral RNAs, proteins, and infectious viral particles in IAV-infected MDCK cells were analyzed. Molecular docking analysis was performed to determine the binding energy of PGG and GE for IAV proteins. To investigate in vivo antiviral activity, IAV-infected mice were treated intranasally or intragastrically with ESE, PGG, or GE.ESE and its gallate main ingredients (PGG and GE) strongly inhibited the production of viral RNAs, viral proteins, and infectious viral particles in vitro. Also through the viral attachment on cells, polymerase activity, signaling pathway, we revealed the ESE, PGG, and GE inhibit multiple steps of IAV replication. Molecular docking analysis revealed that PGG and GE could interact with 12 key viral proteins (M1, NP, NS1 effector domain (ED), NS1 RNA-binding domain (RBD), HA pocket A, HA receptor-binding domain (RBD), NA, PA, PB1, PB2 C-terminal domain, PB2 middle domain, and PB2 cap-binding domain) of IAV proteins with stable binding energy. Furthermore, intranasal administration of ESE, PGG, or GE protected mice from IAV-induced mortality and morbidity. Importantly, oral administration of ESE suppressed IAV replication and the expression of inflammatory cytokines such as IFN-γ, TNF-α, and IL-6 in the lungs to a large extent.ESE and its major components (PGG and PE) exhibited strong antiviral activity in multiple steps against IAV infection in silico, in vivo, and in vitro. Therefore, ESE could be used as a novel natural product derived therapeutic agent to treat influenza virus infection.

Mechanical forces are pervasive in the inflammatory site where dendritic cells (DCs) are activated to migrate into draining lymph nodes. For example, fluid shear stress modulates the movement patterns of DCs, including directness and forward migration indices (FMIs), without chemokine effects. However, little is known about the effects of biomechanical forces on the activation of DCs. Accordingly, here we fabricated a microfluidics system to assess how biomechanical forces affect the migration and activity of DCs during inflammation. Based on the structure of edema, we proposed and experimentally analyzed a novel concept for a microchip model that mimicked such vascular architecture. The intensity of shear stress generated in our engineered chip was found as 0.2–0.6 dyne/cm2 by computational simulation; this value corresponded to inflammation in tissues. In this platform, the directness and FMIs of DCs were significantly increased, whereas the migration velocity of DCs was not altered by shear stress, indicating that mechanical stimuli influenced DC migration. Moreover, DCs with shear stress showed increased expression of the DC activation markers MHC class I and CD86 compared with DCs under static conditions. Taken together, these data suggest that the biomechanical forces are important to regulate the migration and activity of DCs.

Fermented soybean products are gaining attention in the food industry owing to their nutritive value and health benefits. In this study, we performed genomic analysis and physiological characterization of two Debaryomyces spp. yeast isolates obtained from a Korean traditional fermented soy sauce "ganjang". Both Debaryomyces hansenii ganjang isolates KD2 and C11 showed halotolerance to concentrations of up to 15% NaCl and improved growth in the presence of salt. Ploidy and whole-genome sequencing analyses indicated that the KD2 genome is haploid, whereas the C11 genome is heterozygous diploid with two distinctive subgenomes. Interestingly, phylogenetic analysis using intron sequences indicated that the C11 strain was generated via hybridization between D. hansenii and D. tyrocola ancestor strains. The D. hansenii KD2 and D. hansenii-hybrid C11 produced various volatile flavor compounds associated with butter, caramel, cheese, and fruits, and showed high bioconversion activity from ferulic acid to 4-vinylguaiacol, a characteristic flavor compound of soybean products. Both KD2 and C11 exhibited viability in the presence of bile salts and at low pH and showed immunomodulatory activity to induce high levels of the anti-inflammatory cytokine IL-10. The safety of the yeast isolates was confirmed by analyzing virulence and acute oral toxicity. Together, the D. hansenii ganjang isolates possess physiological properties beneficial for improving the flavor and nutritional value of fermented products.

Chios mastic gum (CMG), a resin of the mastic tree (Pistacia lentiscus var. chia), has been used to treat multiple disorders caused by gastrointestinal malfunctions and bacterial infections for more than 2500 years. However, little is known about CMG’s antiviral activity. CMG is known to influence multiple cellular processes such as cell proliferation, differentiation and apoptosis. As virus replication is largely dependent on the host cellular metabolism, it is conceivable that CMG regulates virus infectivity. Therefore, in this study, we evaluated CMG’s potential as an antiviral drug to treat influenza A virus (IAV) infection. CMG treatment dramatically reduced the cytopathogenic effect and production of RNAs, proteins and infectious particles of IAV. Interestingly, CMG interfered with the early stage of the virus life cycle after viral attachment. Importantly, the administration of CMG greatly ameliorated morbidity and mortality in IAV-infected mice. The results suggest that CMG displays a potent anti-IAV activity by blocking the early stage of viral replication. Thus, mastic gum could be exploited as a novel therapeutic agent against IAV infection.